LTB4 is a potent pro-inflammatory lipid mediator derived from arachidonic acid through the 5-lipoxygenase signaling pathway. LTB4 is produced by multiple cell types such as neutrophils, monocytes, macrophases, keratinocytes, lymphocytes and mast cells. It functions as a chemoattractant and as an activator of neutrophil cells. It has been shown that LTB4 effects its action through the agonism of G-protein coupled receptors BLT-1 and BLT-2. (Prostaglandins, Leukotrienes and Essential Fatty Acids 69, 2003, 123-134. )
LTB4 is considered to be an important mediator of acute and chronic inflammatory diseases. Increased levels of LTB4 have been detected in the lungs of patients with severe asthma and COPD. Thus, it is anticipated that an effective inhibitor of the action of LTB4 and BLT-1 and -2 would provide effective therapy for the treatment of inflammatory conditions such as asthma and COPD.
A need exists in the art for LTB4 inhibitors that have efficacy for the treatment of diseases such as COPD.